title: The epithelium specific cell cycle regulator 14-3-3sigma is required for preventing entry into mitosis following ultraviolet B.
abstract: BACKGROUND
  Deoxyribonucleic acid damage activates cell cycle checkpoints in order to maintain genomic stability. We assessed the role of different checkpoint genes in response to ultraviolet B irradiation.
  
  
  METHODS
  Cell lines expressing a dominant negative mutant of ataxia telangiectasia and Rad3 related (Atr) protein or overexpressing Cdc25A, cells deficient for 14-3-3σ, Nijmegen breakage syndrome (Nbs), or Ataxia telangiectasia mutated (Atm) were treated with ultraviolet B (UVB) and harvested after 12 h, 24 h, or 48 h for analysis by flow cytometry.
  
  
  RESULTS
  Functional loss of Atm, Atr, or Nbs did not result in a significant alteration of the cell cycle profile. Overexpression of Cdc25A led to a delayed arrest at the G1/S transition in response to low doses of UVB. Loss of 14-3-3σ, a negative cell cycle regulator and downstream target of p53, caused a transient arrest at the G2/M boundary.
  
  
  CONCLUSIONS
  Loss of 14-3-3σ sensitizes cells to UVB. After a transient cell cycle arrest, 14-3-3σ-deficient cells die by undergoing mitotic catastrophe. Cdc25A overexpression causes a delayed arrest in response to low doses of UVB. After higher doses, Cdc25A is no longer able to overrun the checkpoint. Atm, Atr, or Nbs are not essential for the checkpoint response to UVB, suggesting the existence of redundant signaling pathways.
authors.affiliation: Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Vogel
authors.forename: Thomas
authors.initials: T
authors.lastname: Herzinger
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D005095:Exoribonucleases; C413442:SFN protein, human; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: 14-3-3σ; UVB; carcinogenesis; cell cycle checkpoint; genomic stability